Journal
CIRCULATION
Volume 114, Issue 10, Pages 1020-1027Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.105.600353
Keywords
extracellular matrix; matrix metalloproteinases; myocardial infarction; remodeling
Funding
- NCRR NIH HHS [MO1-RR-01070-251] Funding Source: Medline
- NHLBI NIH HHS [P01-HL-48788, R01-HL-59165] Funding Source: Medline
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Background - Changes in matrix metalloproteinase (MMP) and tissue inhibitors of MMPs (TIMPs) contribute to left ventricular (LV) remodeling after myocardial infarction (MI). We tested the hypothesis that a specific plasma MMP/TIMP profile would emerge after MI and be associated with the degree of LV dilation. Methods and Results - LV end-diastolic volume and MMP/TIMP plasma profiles were determined in 53 age-matched control subjects and 32 post-MI patients from day 1 through 180 after MI. LV end-diastolic volume increased by > 38% at day 90 after MI (P < 0.05). MMP-9 increased by > 150% from control at day 1 after MI (P < 0.05) and remained elevated. MMP-8 rose to > 120% at day 3 after MI (P < 0.05) and fell to control values by day 5. TIMP-1 increased by > 60% from control at day 1 after MI (P < 0.05), whereas TIMP-2 increased only at later time points. Cardiac-specific TIMP-4 fell by 40% at day 5 after MI and remained reduced. A persistent or elevated MMP-9 at day 5 was accompanied by a 3-fold end-diastolic volume increase at day 28 (P < 0.05). Conclusions - A specific temporal pattern of MMP/TIMPs occurred in post-MI patients that included an early and robust rise in MMP-9 and MMP-8 and a uniform fall in TIMP-4. These findings suggest that a specific MMP/ TIMP plasma profile occurs after MI and holds both prognostic and diagnostic significance.
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